The elimination of THC and its many metabolites (from all routes) occurs via the feces and urine. Metabolites tissues, but less than 1% of an administered dose reaches the brain,. while the . The present section will be restricted to human pharmaco-. kinetics .. There is limited information on the metabolism of CBD. A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans to retrieve all articles reporting pharmacokinetic data of CBD in humans. to report the absolute bioavailability of CBD following other routes in humans, despite i.v . reviewed paper that involved administration of CBD to humans. The route of administration affects the pharmacokinetics of CBD and high.
Routes Human Pharmacokinetics Administration of Upon Various CBD
Compared to many other drugs, analysis of cannabinoids is difficult because THC and OH-THC are highly lipophilic, and are present in very low concentrations in body fluids. Complex specimen matrices, i. Interpreting drug effect, whether therapeutic effect or physical or mental impairment is particularly difficult due to a lack of correlation between drug effect and biologic levels as well as there being a wide variability from person to person, even with the same person at different times.
Prediction models have been proposed for estimation of cannabis exposure but there is controversy in the interpretation of cannabinoid results from blood analysis. THC effects appear rapidly after initiation of smoking. A dose-response relationship has been established for smoked THC and THC plasma concentrations and it is well-established that plasma THC concentrations begin to decline prior to the time of its peak effects.
Individual drug concentrations and ratios of cannabinoid metabolite to parent drug concentration have been suggested as potentially useful indicators of recent use. These findings also likely apply to chronic use of all forms of cannabinoids. Furthermore, studies of drug effect and level of impairment do not correlate well with plasma levels due to differences in acute vs chronic exposure and other individual variables. Detection of cannabinoids in urine is indicative of prior cannabis exposure, but the long excretion half-life of THC-COOH in the body, especially in chronic cannabis users, makes it difficult to predict the timing of past drug use.
As such, a positive urine test for cannabinoids indicates only that THC exposure has occurred. The result does not provide information on the route of administration, the amount of drug exposure, when drug exposure occurred, or the degree of impairment. Oral fluid can be used for monitoring cannabinoid exposure and is being evaluated for the assessment of driving under the influence and for workplace drug testing.
The oral mucosa is exposed to high concentrations of THC during smoking which serves as the source of THC found in oral fluid. Detection times of THC in oral fluid are shorter than in urine, and more indicative of recent cannabis use. Oral-fluid THC concentrations temporally correlate with plasma cannabinoid concentrations and behavioral and physiological effects, but wide intra- and inter-individual variation precludes the use of oral-fluid concentrations as indicators of drug impairment.
Smoking provides a very rapid and efficient means of delivery of cannabanoids from the lungs to the brain which can be intensely pleasurable and strongly reinforcing due to almost immediate drug exposure to the brain and central nervous system CNS.
Depending on the potency of the inhaled product, mean plasma peak THC concentrations have been measured at Furthermore, the clinical effects of THC continue even after plasma levels drop to very low levels. THC is readily absorbed when ingested but absorption is slower compared with smoking, with lower and more-delayed peak THC concentrations. In another study peak THC concentrations ranged from 4. While the THC and other cannabinoids and pharmacologically active cannabis constituents are absorbed directly into the blood and to the brain after smoking, when ingesting cannabis or cannabinoids orally they undergo significant metabolism before reaching the blood and brain.
This metabolism begins in the stomach and gut and continues in the liver before getting to the blood. THC is primarily metabolized to OH-THC, another psychoactive compound that contributes significantly to the psychoactive effects associated with cannabis use. THC concentrations decrease in brain tissue slower than in blood but the slowest THC elimination is seen in fat tissue, where THC may still be present for months after chronic use. Mean peak plasma concentrations of 3.
Due to low bioavailability of oral THC formulations, alternative routes of drug administration, including oromucosal or sublingual dosing and rectal administration, have been developed to improve the amount of delivered cannabinoids.
When THC is ingested orally as compared to smoking, onset of clinical effects are delayed, peak concentrations are lower, and duration of clinical effects generally are longer with a delayed return to baseline.
THC-containing bakery items and foods, i. The THC content depends upon the cannabis-seed-cleaning and oil-filtration processes but hemp oil without THC is available in Louisiana.
The bioavailability of the rectal route is approximately twice that of the oral route due to higher absorption and lower first-pass metabolism by the liver. Rectal administration of 2. Topical administration is another route of cannabinoid dosing that avoids first-pass metabolism and improves THC bioavailability.
Cannabinoids are highly hydrophobic, making transport across the aqueous layer of the skin the rate-limiting step in the diffusion process.
Additional research is planned with combinations of cannabinoids to increase drug absorption and hopefully reduce negative side effects seen with inhalation and oral dosing. Whether people with genetic variants of these enzymes may experience altered effects from cannabinoids is not fully known. One study published in evaluated the impact of the CYP2C9 polymorphisms on the pharmacokinetics of orally administered 9-tetrahydrocannabinol THC.
Therefore, if concomitant drug treatment with CYP3A4 inhibitors e. Therefore, concomitant treatment with strong enzyme inducers e. Again, if concomitant drug treatment with CYP3A4 inducers e.
CBD has been identified as a potent inhibitor of CYP2D6 which may have significant impact on the metabolism of medications that are broken down by CYP2D6, including hydrocodone Norc0, Vicodin, Zohydro, Hysingla and other opioids including tramadol and codeine. As such, use of CBD with tramadol, codeine or hydrocodone may significantly reduce the analgesic effectiveness of these opioids. Other common medications that may be affected include antidepressants. Also, CYP3A5 is a major isoform of CYP3A found in extrahepatic tissues that plays an important role in the metabolism of endogenous and exogenous compounds in these tissues.
Thus, the inhibition of CYP3A5 by CBD may cause interactions with other medications and may also disturb normal metabolism of endogenous compounds.
National Academy of Sciences. The Health Effects of Cannabis and Cannabinoids: This website appears to be good resource for exploring medical marijuana. Not very practical and greatly increases the chance of adverse effects.
Depending on the matrix in which the cannabinoids are delivered there may be limited penetration beyond the dermal layer and into the blood. Pure Ratios offers patches for localized relief that do not penetrate the dermal layer and hence does not produce psychoactive effects.
This route of administration greatly increases bioavailability because it bypasses the liver. Pure Ratios has also developed transdermal patches that provide extended relief. For example, if a patient is new to cannabis it is advantageous to start with a higher CBD to THC ratio to avoid adverse effects, especially if the route of administration is inhalation.
For example, in an inexperienced cannabis user this dosage could induce adverse effects, especially if administered orally for reasons mentioned above. As mentioned, some testing labs consider a standard dose of cannabinoids as 10 mg. While this serves as a good conservative measure it is certainly not a one size fits all.
Studies have demonstrated that cannabinoid receptor density can fluctuate rapidly in a short window of time making tolerance one of the most important factors in dosing .
Further adding to the complexity of cannabis dosing is the biphasic response of the cannabinoids. For example, at low doses THC produces and anxiety-relieving effect and induces anxiety at higher doses . Pure Ratios has developed product lines that have a treatment plan in mind. Pure Ratios also offers vapor lines that allow for that baseline to be titrated with varying cannabinoid ratios. These blends are also infused with premium essential oils from a variety of healing plants for maximum therapeutic benefit.
Biol Psychiatry Cogn Neurosci Neuroimaging. Patients Out of Time Presentation.
Routes of Administration and Dosing for Cannabinoids
Human Pharmacokinetics and Adverse Effects of Pulmonary and After inh and iv administration, THC plasma peaks were observed 5 min post-drug min after inh and 22 and 24 min after iv administration for THC and CBD, respectively. All other chemicals and solvents were of the best available grade. Discusses the various ways of administering cannabinoids, dosing guidance, and the far too much depending on the individuals needs and prior cannabis experience. Not all routes of administration are equal in terms of bioavailability due to a higher CBD to THC ratio to avoid adverse effects, especially if the route of. routes reported for CBD metabolites and their close structural analogs are also catalogued. Human Pharmacokinetics of CBD Upon. Various Administration.